Site-directed mutagenesis of Saccharomyces cerevisiae beta-tubulin: interaction between residue 167 and benzimidazole compounds.

Abstract:

:Benzimidazoles are widely used as anthelmintic agents and systemic fungicides. In susceptible organisms, benzimidazoles bind to beta-tubulin and block microtubule polymerization. To further characterize this interaction, site-directed mutagenesis followed by gene replacement was used to change Saccharomyces cerevisiae beta-tubulin residue Phe-167 to Tyr. Consistent with previous studies, this mutation resulted in at least 3-4-fold decreased sensitivity to the benzimidazole derivatives carbendazim and nocodazole. The Tyr-167 mutant was cold sensitive, implying a direct effect on benzimidazole binding rather than a nonspecific increase in microtubule stability. Surprisingly, the mutant had 8-fold increased sensitivity to the derivative benomyl, which is structurally identical to carbendazim except at position 1. This suggests that residue 167 interacts with benzimidazoles in the vicinity of the 1-position.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Li J,Katiyar SK,Edlind TD

doi

10.1016/0014-5793(96)00334-1

subject

Has Abstract

pub_date

1996-04-29 00:00:00

pages

7-10

issue

1-2

eissn

0014-5793

issn

1873-3468

pii

0014-5793(96)00334-1

journal_volume

385

pub_type

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